2.1 Prostate Cancer
Prostate cancer is the most common cancer for males in the United States (excluding skin cancer), accounting for 32% of all newly diagnosed cancers, and it is the second leading cause of death by cancer (after lung cancer), accounting for 13% of cancer deaths in men. Using pathological data, “The Principles and Practice of Oncology” published by the Shangdong Science Publisher reported that the prevalence of prostate cancer increases substantially with each decade of life from the 50s: one-third of men who are sixty-years and older have latent prostate cancer tissue; one-half of men who are seventy-years and older have latent prostate cancer tissue; and three-quarters of men who are eighty-years and older have with latent prostate cancer. The incidence rate is 107.7 per 100,000 for the male population, 107.3 per 100,000 white males, and 145.8 per 100,000 nonwhite males (Miller et al., 1993, National Cancer Institute, NIH Pub. No. 93-2789). The incidence of prostate cancer is less common in Asian and American Indian men. According to the American Cancer Society, in 2000, an estimated 180,400 men in the United States were diagnosed with prostate cancer and almost 32,000 men died of the disease.
The recognized risk factors for prostate cancer include age, race, genetics, and environment. A family history of prostate cancer may also increase an individual's risk of developing the disease. The incidence rates of prostate cancer have nearly doubled from rates 20 years ago. One possible explanation is that due to the decline in heart disease mortality in recent decades, more men are living to older ages, when prostate cancer risk is highest. Studies also suggest that a high-fat diet may increase the risk of prostate cancer, and that a diet rich in vegetables, particularly cruciferous vegetables (e.g., broccoli, cabbage, cauliflower, kale, collard and mustard greens, horseradish, kohlrabi, Brussels sprouts, broccoli rabe, radishes, turnip, rutabaga, and watercress) is associated with a reduced risk of prostate cancer. Some studies have observed that men who have vasectomies are somewhere between 1.5 to 2.0 times more likely to have a later diagnosis of prostate cancer than men who have not had a vasectomy.
While many men experience no symptoms of prostate cancer before it is discovered, others may notice frequent urination (especially at night) or an inability to urinate, trouble starting or holding back urine, pain during ejaculation or urination, a weak or interrupted urine flow, blood in the semen or in the urine, or frequent pain or stiffness in the lower back, hips or upper thighs. However, these symptoms are also observed with a common, non-cancerous condition called benign prostatic hyperplasia (BPH), which is an enlargement of the prostate gland. Two frequently used screening tests are digital rectal examination (DRE) and blood test, which detects the amount of prostate specific antigen (PSA) circulating in the blood. Nearly 80 percent of all prostate tumors are diagnosed at an early stage—when they are still in the local or regional stages. For these patients, the five-year survival rate is 100 percent.
Most prostate tumors are adenocarcinomas. The staging of prostate cancer is based on the revised criteria of TNM staging by the American Joint Committee for Cancer (AJCC) published in 1988. Staging is the process of describing the extent to which cancer has spread from the site of its origin. It is used to assess a patient's prognosis and to determine the choice of therapy. The stage of a cancer is determined by the size and location in the body of the primary tumor, and whether it has spread to other areas of the body. Staging involves using the letters T, N and M to assess tumors by the size of the primary tumor (T); the degree to which regional lymph nodes (N) are involved; and the absence or presence of distant metastases (M)—cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes. Each of these categories is further classified with a number 1 through 4 to give the total stage. Once the T, N and M are determined, a “stage” of I, II, III or IV is assigned. Stage I cancers are small, localized and usually curable. Stage II and III cancers typically are locally advanced and/or have spread to local lymph nodes. Stage IV cancers usually are metastatic (have spread to distant parts of the body) and generally are considered inoperable.
Treatment options for prostate cancer include surgery, radiation therapy, hormone therapy, chemotherapy, and vaccines comprising monoclonal antibodies that blocks growth-factor receptors on the surface of cancer cells and thereby, prevent the activation and growth of cancer cells. Surgery is the most common treatment for prostate cancer and involves removing the prostate (a procedure called radical prostatectomy), as well as some tissue surrounding it. During surgery, a sample of the lymph nodes in nearby tissue is usually removed to better assess whether the cancer has spread beyond the prostate. In general, 75 percent of men treated with surgery will live out their lives without recurrence of their cancer. However, a permanent side effect of surgery is infertility and possibly urinary incontinence and impotence.
Radiation therapy is the second most common treatment. For the treatment of prostate cancer, the high-energy rays can be delivered by two basic methods: external beam (similar to an x-ray) or brachytherapy (internal radiation delivered with implanted radioactive seeds). Fatigue is a possible side effect of radiation therapy, but it gradually ceases after treatment is completed. Some men may also experience impotence, bowel problems, urinary problems, and rectal discomfort or bleeding. Depending on how extensive the cancer is or how big the prostate has grown, hormone therapy may be used before radiation therapy to help shrink the size of the tumor, thereby making it easier to treat. Hormone therapy decreases the amount of male hormone testosterone in the body, which can promote the growth of cancer cells. Drugs that are used for hormone therapy include leuprolid acetate (Lupron Depot®), goserelin acetate implant (Zoladex®), bicalutamide (Casodex®), and flutamide (Eulexin®). Side effects include gynecomastia (development of breast tissue).
Chemotherapy is used primarily in cases where the disease has spread outside the prostate and where hormonal treatments alone are no longer effective in preventing tumor growth. Potential side effects include nausea and vomiting, loss of hair, low blood cell counts, and fatigue. Many chemotherapeutic drugs have been tried in the past as single agents for the palliation of prostate cancer, but the results were generally disappointing. Nevertheless, the role of chemotherapy in the management of prostate cancer is continually evolving. Oftentimes, chemotherapy with radiation in adjunct to surgery is used. In general, chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease (Ali et al., 2000, Oncology 14(8):1223–30). Unfortunately, the high initial response rates to first line chemotherapy does not appear to translate into a survival benefit (Kohno and Kitahara, 2001, Gan To Kagaku Ryoho 28(4):448–53). Moreover, there are many undesirable side effects associated with chemotherapy such as temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea. Active chemotherapeutic agents include mitoxantrone, prednisone, paclitaxel, docetaxel, estramustine, adriamycin, estramustine phosphate (Emcyt®), and mitoxantrone (Novantrone®).
The identification of active chemotherapeutic agents against cancers traditionally involved the use of various animal models of cancer. The mouse has been one of the most informative and productive experimental system for studying carcinogenesis (Sills et al., 2001, Toxicol Letters 120:187–198), cancer therapy (Malkinson, 2001, Lung Cancer 32(3):265–279; Hoffman R M., 1999, Invest New Drugs 17(4):343–359), and cancer chemoprevention (Yun, 1999, Annals NY Acad Sci. 889:157–192). Cancer research started with transplanted tumors in animals which provided reproducible and controllable materials for investigation. Pieces of primary animal tumors, cell suspensions made from these tumors, and immortal cell lines established from these tumor cells propagate when transplanted to animals of the same species.
To transplant human cancer to an animal and to prevent its destruction by rejection, the immune system of the animal are compromised. While originally accomplished by irradiation, thymectomy, and application of steroids to eliminate acquired immunity, nude mice that are athymic congenitally have been used as recipients of a variety of human tumors (Rygaard, 1983, in 13th International Cancer Congress Part C, Biology of Cancer (2), pp37–44, Alan R. Liss, Inc., NY; Fergusson and Smith, 1987, Thorax, 42:753–758). While the athymic nude mouse model provides useful models to study a large number of human tumors in vivo, it does not develop spontaneous metastases and are not suitable for all types of tumors. Next, the severe combined immunodeficient (SCID) mice is developed in which the acquired immune system is completely disabled by a genetic mutation. Human lung cancer was first used to demonstrate the successful engraftment of a human cancer in the SCID mouse model (Reddy S., 1987, Cancer Res. 47(9):2456–2460). Subsequently, the SCID mouse model have been shown to allow disseminated metastatic growths for a number of human tumors, particularly hematologic disorders and malignant melanoma (Mueller and Reisfeld, 1991, Cancer Metastasis Rev. 10(3): 193–200; Bankert et al., 2001, Trends Immunol. 22:386–393). With the recent advent of transgenic technology, the mouse genome has become the primary mammalian genetic model for the study of cancer (Resor et al., 2001, Human Molec Genet. 10:669–675).
While surgery, chemotherapeutic agents and radiation are useful in the treatment of prostate cancer, there is a continued need to find better treatment modalities and approaches to manage the disease that are more effective and less toxic, especially when clinical oncologists are giving increased attention to the quality of life of cancer patients. The present invention provides an alternative approach to cancer therapy and management of the disease by using an oral composition comprising yeasts.
2.2 Yeast-Based Compositions
Yeasts and components thereof have been developed to be used as dietary supplement or pharmaceuticals. However, none of the prior methods uses yeast cells which have been cultured in an electromagnetic field to produce a product that has an anti-cancer effect. The following are some examples of prior uses of yeast cells and components thereof:
U.S. Pat. No. 6,197,295 discloses a selenium-enriched dried yeast product which can be used as dietary supplement. The yeast strain Saccharomyces boulardii sequela PY 31 (ATCC 74366) is cultured in the presence of selenium salts and contains 300 to about 6,000 ppm intracellular selenium. Methods for reducing tumor cell growth by administration of the selenium yeast product in combination with chemotherapeutic agents is also disclosed.
U.S. Pat. No. 6,143,731 discloses a dietary additive containing whole β-glucans derived from yeast, which when administered to animals and humans, provide a source of fiber in the diet, a fecal bulking agent, a source of short chain fatty acids, reduce cholesterol and LDL, and raises HDL levels.
U.S. Pat. No. 5,504,079 discloses a method of stimulating an immune response in a subject utilizing modified yeast glucans which have enhanced immunobiologic activity. The modified glucans are prepared from the cell wall of Saccharomyces yeasts, and can be administered in a variety of routes including, for example, the oral, intravenous, subcutaneous, topical, and intranasal route.
U.S. Pat. No. 4,348,483 discloses a process for preparing a chromium yeast product which has a high intracellular chromium content. The process comprises allowing the yeast cells to absorb chromium under a controlled acidic pH and, thereafter inducing the yeast cells to grow by adding nutrients. The yeast cells are dried and used as a dietary supplement.
Citation of documents herein is not intended as an admission that any of the documents cited herein is pertinent prior art, or an admission that the cited documents are considered material to the patentability of the claims of the present application. All statements as to the date or representations as to the contents of these documents are based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.